Fariba Behbod, Pharm.D, Ph.D.

I am a Full Professor in the Division of Cancer and Developmental Biology within the Department of Pathology and Laboratory Medicine and a full member of the Cancer Research Institute at the University of Kansas Medical Center (KUMC). I have a dual doctorate degree in Clinical Pharmacy and Integrative Biology and Pharmacology. I am also a member of KUMC’s Ph.D. and M.D./Ph.D. advisory and admissions committees. My post-doctoral training in the laboratory of Dr. Jeffrey M. Rosen was funded by NCI (NCI-NRSA; 2003-2006) and focused on studying the role of stem cells in mammary gland development and breast cancer. Towards the end of my post-doctoral training, I became interested in studying the molecular mechanisms of DCIS invasive progression. In order to pursue this goal, I joined the research efforts of Drs. Medina and Allred, both long-term collaborators of my mentor and renowned scientists in the field of human breast premalignancy. To obtain independent funding, I applied for an NIH sponsored career development award (K99/R00) for which Drs. Allred, Medina and Rosen served as co-mentors. The successful funding of our project led to the first development of an orthotopic model known as mouse-intraductal (MIND). With the notion that DCIS initiates inside the breast ducts, we devised the MIND model, which involves intraductal injection of human primary DCIS cells and cell lines inside the mammary ducts of immunocompromised mice. This model is now nationally and internationally known as the most realistic model of breast cancer progression from non-invasive to malignant disease.

The focus of our research is Human ductal carcinoma in situ (DCIS). DCIS are the most common form of human non-invasive breast cancers. It is currently estimated that about 60% of DCIS would not progress to invasive ductal carcinoma (IDC) if left untreated, but our inability to predict progression has resulted in unnecessary treatment for many women diagnosed each year. To study DCIS, we developed a novel animal model, referred to as mouse-intraductal model (MIND) that utilizes intraductal (ID) injection of primary human DCIS cells into the mammary ducts of immunocompromised mice. We were the first to demonstrate the success of the MIND model in mimicking the natural evolution of human DCIS in mice. This was made possible through a very productive collaboration that we established with local clinicians to obtain a large number of patient biopsy and surgical specimens. As such, MIND model is most suitable in predicting DCIS with invasive potential thus facilitating the development of future clinically useful biomarkers of high risk DCIS to help prevent overtreatment. Recently, we have further improved the translation application of our MIND model by engraftment of mice using patient’s own hematopoietic stem cells (HSC). This advancement will enable the future studies related to immune cell regulation of DCIS progression.

By studying the molecular changes associated with DCIS to IDC transition using our novel models, we discovered BCL9 and validated its role in promotion of DCIS invasive progression. We have now accumulated exciting new preliminary data that BCL9/STAT3 protein complexes on enhancers result in enhancer activation and transcription of target genes that regulate DCIS invasive progression including integrin avb3 and MMP16. We have also demonstrated the efficacy of rosemary extract and its active ingredient carnosic acid in inhibition of DCIS invasive progression by targeting BCL9 for degradation. The goal of the current project is to study the mechanism by which carnosic acid targets BCL9 for degradation, validate the role of BCL9/STAT3 as molecular biomarkers of aggressive DCIS and finally study the mechanism by which BCL9 mediated cellular co-expression of integrin avb3/MMP16 drive DCIS malignant progression.
I am very proud that my laboratory continues to be a home for undergraduate, graduate, pre-med students and post-doctoral fellows interested in learning and/or pursuing biomedical research. I have served as a mentor on six KINBRE and three KUCC summer student scholarships, one F31, one Center of Excellence, one K22, and two DOD awards.